PROJECT SUMMARY The objective of this continuation project, submitted in response to PA-16-242 (Bioengineering Research Grants), is to study the mechanism of presbyopia, the progressive age-related loss of the ability to see clearly at near distances. The long-term goal is to enable the development of effective strategies to restore accommodation in presbyopes. The project addresses two critical barriers to progress in the field: a) the need for a better understanding of the factors contributing to presbyopia, particularly the role of the ciliary muscle and b) the need for technologies that can objectively assess the outcomes of procedures to restore accommodation in a clinical setting. The project has two specific aims: Aim 1: To develop a high speed integrated multimodal accommodation biometry system The accommodation biometry system will build on a first generation of the system that was developed in the previous project period. The system will combine a dynamic autorefractor and two optical coherence tomography systems in an integrated hardware and software platform that will enable acquisition of data by a single user in a clinical setting. It will enable high-speed and precisely synchronized measurements of the dynamics of ciliary muscle movement, changes in shape of the crystalline lens, and changes in refraction in response to pulse-step and ramp stimuli of accommodation. Aim 2: To characterize the dynamics of the ciliary muscle with accommodation and age The accommodation biometry system will be used to quantify the dynamics of the ciliary muscle and the resulting changes in crystalline lens shape in participants with ages ranging from 14 to 74 years and in cataract surgery patients who will be imaged pre-operatively and one month after IOL implantation. The data will be analyzed to test the predictions that a) there are age- related changes in the dynamics of the ciliary muscle and its interaction with the lens in the age range leading to presbyopia; b) presbyopia is associated with alterations in the ciliary muscle morphology that may affect the ability to restore accommodation; and c) replacement of the natural lens with an artificial implant alters the ability of the ciliary muscle to respond to an accommodation stimulus. The project will have a broad impact on the field of presbyopia research. It will produce new technology to image the ciliary muscle of the eye and its interaction with the lens in real-time during accommodation. It will also generate new knowledge on the causes of presbyopia that will form a sound physiological basis for the development and optimization of new procedures and implants designed to restore accommodation.